Enhancing Rehabilitation After Stroke (Enhance)

Inclusion Criteria:

1. male or female;
2. aged 18 or older;
3. new ischemic stroke within the preceding 30 days; and
4. admitted to the an inpatient facility of the UPMC Institute for Rehabilitation and Research for post-stroke rehabilitation.

Exclusion Criteria:

1. primary hemorrhagic stroke;
2. current use of a cholinomimetic drug including tacrine, donepezil, galantamine, and rivastigmine;
3. contraindication to AchEi therapy including bradycardia (< 50 bpm), severe asthma or COPD requiring nebulized medication, and active upper GI bleed or untreated gastric ulcer;
4. myocardial infarction, poorly controlled congestive heart failure, or coronary bypass surgery within the last 3 months;
5. current required use of an anticholinergic medication (e.g., for bladder spasm);
6. current aphasia severe enough to prevent valid neuropsychiatric assessment (e.g., a score < 9 on the Token Test, part I and a score of < 14 (or <80% accuracy) on the repetition task of the Boston Diagnostic Aphasia Examination);
7. current Major Depressive Episode AND HRSD > 20;
8. current active suicidal ideation, plan, or intent;
9. current mania or hypomania;
10. current psychosis;
11. meeting DMS-IV TR alcohol or substance abuse or dependence criteria within the preceding 3 months;
12. subject and/or family informant do not speak English;
13. history of a progressive or unstable CNS disease (e.g., multiple sclerosis, Parkinson's disease, HIV with CNS involvement);
14. medically unstable (determined by review of the subject's medical status with the treating (clinical) physician and by review of standard blood tests); and
15. history of sensitivity to donepezil;
16. for potential subjects without a pacemaker or implantable defibrillator, exclusion criteria will include (a) ECG evidence of second or third degree heart block ( b ) ECG evidence of a tri-fascicular block (LBBB and 1st degree AV Block; RBBB, left anterior or left posterior hemiblock, and 1st degree AV block) or ( c ) history of syncope within 1 year with a RBBB or a LBBB.
17. For females of child-bearing age, current pregnancy, plan to become pregnant while on study drug, or refusal to avoid pregnancy while on study drug.
18. For females of child-bearing age, current breast feeding.
19. suicidal attempt in the past one year,
20. an inpatient admission for depression in the past one year